Impaired intracellular trafficking of adeno-associated virus type 2 vectors limits efficient transduction of murine fibroblasts

被引:126
作者
Hansen, J
Qing, K
Kwon, HJ
Mah, C
Srivastava, A
机构
[1] Indiana Univ, Sch Med, Dept Microbiol & Immunol, Indianapolis, IN 46202 USA
[2] Indiana Univ, Sch Med, Walther Oncol Ctr, Indianapolis, IN 46202 USA
[3] Indiana Univ, Sch Med, Dept Med, Div Hematol Oncol, Indianapolis, IN 46202 USA
[4] Walther Canc Inst, Indianapolis, IN 46202 USA
[5] Univ Florida, Coll Med, Gene Therapy Ctr, Gainesville, FL 32610 USA
关键词
D O I
10.1128/JVI.74.2.992-996.2000
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Although adeno-associated virus type 2 (AAV) has gained attention as a potentially useful alternative to the more commonly used retrovirus- and adenovirus based vectors for human gene therapy, efficient gene transfer and transgene expression by AAV vectors require that the following two obstacles be overcome. First, the target cell must express the receptor and the coreceptor for AAV infection, and second, the cell must allow for viral second-strand DNA synthesis. We now describe a third obstacle, impaired intracellular trafficking of AAV to the nucleus, which results in the lack of transgene expression in murine fibroblasts which do express the AAV receptor and the coreceptor and which are permissive for viral second-strand DNA synthesis. We document that AAV vectors bind efficiently and gain entry successfully into NIH 3T3 cells, but trafficking into the nucleus is significantly impaired in these cells. In contrast, viral trafficking to the nucleus in cells known to be efficiently transduced by AAV vectors is both rapid and efficient. The demonstration of yet another obstacle in AAV-mediated gene transfer has implications for the optimal use of these vectors in human gene therapy.
引用
收藏
页码:992 / 996
页数:5
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